Hendrikse N H, Vaalburg W
PET Center, University Hospital of Groningen, The Netherlands.
Novartis Found Symp. 2002;243:137-45; discussion 145-8, 180-5. doi: 10.1002/0470846356.ch10.
P glycoprotein (Pgp) is expressed on cell membranes of various organs in the body, such as the capillary endothelial cells of the brain. Furthermore, Pgp can also be expressed on the cell membrane of tumour cells. Because of Pgp-mediated efflux, tissue levels of several Pgp substrates are lower than in Pgp-negative tissues. Drug levels in Pgp-expressing organs may be increased by modulation of this Pgp-facilitated transport with several compounds, such as cyclosporin A. Up to now, the presence of drug efflux pumps in tissues could only be examined at the mRNA and protein level. However, this gives no insight into the important question of the functionality of these drug efflux pumps. Information about the transport function of Pgp and the effect of modulating this function may improve the therapeutic treatment of these patients. Positron emission tomography (PET) gives us a unique opportunity to study non-invasively (patho)physiological dynamic processes in vivo. We have therefore developed and validated a method for studying Pgp-mediated transport and its modulation in vivo with PET.
P糖蛋白（Pgp）在机体各器官的细胞膜上表达，如脑毛细血管内皮细胞。此外，Pgp也可在肿瘤细胞的细胞膜上表达。由于Pgp介导的外排作用，几种Pgp底物的组织水平低于Pgp阴性组织。通过用几种化合物（如环孢素A）调节这种由Pgp促进的转运，可提高Pgp表达器官中的药物水平。到目前为止，组织中药物外排泵的存在只能在mRNA和蛋白质水平上进行检测。然而，这无法深入了解这些药物外排泵功能这一重要问题。关于Pgp转运功能及其调节作用的信息可能会改善这些患者的治疗。正电子发射断层扫描（PET）为我们提供了一个在体内非侵入性研究（病理）生理动态过程的独特机会。因此，我们已经开发并验证了一种用PET在体内研究Pgp介导的转运及其调节的方法。
